Abnormal control of an alternative splicing mechanism has been reported in various diseases such as neurodegenerative disease, amyotrophic lateral sclerosis and cancer. Particularly in cancer, cancer-specific splicing variants produced by abnormal alternative splicing have been shown to play an important role in cancer survival and invasion. In recent years, it has been shown that spliceosome constituent factors such as SF3B1, SRSF2 and U2AF1 are mutated with high frequency in the osteomyelodysplasia syndrome. These findings indicate that control of an alternative splicing mechanism plays an important role in cancer.
CLK family kinase is a type of bispecific protein kinase retaining both serine/threonine kinase activity and tyrosine kinase activity, and include four types of kinase: CLK1 to CLK4. CLK phosphorylates SR proteins such as SRSF1 to control localization of the proteins, so that a splicing regulation mechanism by SR proteins is controlled. It has been shown that by regulating alternative splicing by inhibition of CLK kinase activity, signals essential for survival of cancer can be hindered to inhibit growth of cancer cells. In addition, CLK2 has been shown to act as an oncogene in breast cancer. Therefore, inhibition of kinase activity of CLK may be a promising treatment for cancer.
Patent Literatures 1 and 2 disclose a fused heterocyclic compound as a compound having a tyrosine kinase inhibitory action. Patent Literatures 3 and 4 disclose a fused heterocyclic compound having other pharmacological activities.